Insects are able to respond to microbial infections by defensive actions of the hemocytes (blood cells) and by synthesis of antibacterial proteins by the fat body. The mechanisms by which nonself is recognized by insect cells are unknown. A bacteria-induced protein of M(r) = 48,000 isolated from the hemolymph of the tobacco hornworm, Manduca sexta, has been shown by analysis of its cDNA sequence to be a member of the immunoglobulin gene superfamily. The long-term objective of this proposal is to understand the role of proteins related to immunoglobulins in the insect immune system. Specific aims are: 1) Isolation and sequencing of cDNA and genomic clones for members of the immunoglobulin-related hemolymph protein (IRHP) family in Manduca; 2) Regulation of IRHP gene expression; 3) Identification of IRHP functions; 4) Studies of immunoglobulin-related proteins expressed in hemocytes; 5) Studies on IRHP in Drosophila. The study of insect proteins related to immunoglobulins may yield information relevant to the understanding of insects as vectors of human and animal diseases and also contribute to knowledge on the evolution of the immunoglobulin gene superfamily.